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Background: Experimental long-term carcinogenicity bioassays conducted on rats and mice proved that ionizing radiation can induce a variety of tumor types. However few studies have been conducted on rats., Methods: This report deals with the effects of γ-radiation in groups of 416-1,051 6-weeks old Sprague-Dawley rats exposed to 0, 0.1, 1, or 3 Gy of γ-radiation delivered in a single acute exposure. The experiment lasted for the animals' lifespan and all were necropsied and underwent full histopathological evaluation., Results: The results confirm the dose-related carcinogenic effects of γ-radiation for several organs and tissues. Moreover they indicate that exposure to 0.1 Gy induces a statistically significant increased incidence in Zymbal gland carcinomas and pancreas islet cell carcinomas in females., Conclusions: Our data show that exposure to γ-radiation induces carcinogenic effects at all tested doses., (© 2014 Wiley Periodicals, Inc.)

Aspartame (APM) is an artificial sweetener used since the 1980s, now present in >6,000 products, including over 500 pharmaceuticals. Since its discovery in 1965, and its first approval by the US Food and Drugs Administration (FDA) in 1981, the safety of APM, and in particular its carcinogenicity potential, has been controversial. The present commentary reviews the adequacy of the design and conduct of carcinogenicity bioassays on rodents submitted by G.D. Searle, in the 1970s, to the FDA for market approval. We also review how experimental and epidemiological data on the carcinogenic risks of APM, that became available in 2005 motivated the European Commission (EC) to call the European Food and Safety Authority (EFSA) for urgent re-examination of the available scientific documentation (including the Searle studies). The EC has further requested that, if the results of the evaluation should suggest carcinogenicity, major changes must be made to the current APM specific regulations. Taken together, the studies performed by G.D. Searle in the 1970s and other chronic bioassays do not provide adequate scientific support for APM safety. In contrast, recent results of life-span carcinogenicity bioassays on rats and mice published in peer-reviewed journals, and a prospective epidemiological study, provide consistent evidence of APM's carcinogenic potential. On the basis of the evidence of the potential carcinogenic effects of APM herein reported, a re-evaluation of the current position of international regulatory agencies must be considered an urgent matter of public health., (© 2014 Wiley Periodicals, Inc.)

Unlabelled: Dystonia is a central motor processing neurological disorder characterized by abnormal, often action-induced, involuntary movements or uncontrolled spasms., Aim: To compare patients with the diagnoses of focal and segmental adductor laryngeal dystonia at the Neurolarynx Outpatient Clinic of the Federal University of São Paulo., Materials and Methods: A clinical retrospective study of data collected from patient registries from 2003 to 2009., Results: Of 34 patients, 25 presented focal dystonia and 9 presented segmental dystonia. There were 30 females (88. 2%) and 4 males (11. 8%). A relation with a traumatic event was reported in 11 cases (32. 4%). Vocal tremor was observed in 21 patients (61. 8%). The mean age at onset, the age at diagnosis, and time between the onset and the diagnosis were respectively 55, 61. 3 and 6. 3 years. There was no statistical difference between patients with focal laryngeal adductor dystonia and segmental dystonia in the study data., Conclusions: There were no statistical differences among patients with focal adductor laryngeal dystonia and segmental dystonia relating to age of onset, age of diagnosis, gender, time between onset and diagnosis, presence of associated tremor, and relation to trauma.

Although the latency between the initiation of thyroarytenoid electrical activity and the onset of phonation generally is increased in patients with adductor laryngeal dystonia, there is disagreement about whether there is overlap of latency values in these patients and normal subjects. The goal of this article was to compare the severity of dysphonia with the latency between electrophysiological activation of the thyroarytenoid muscle (TA) and the onset of phonation in patients with adductor laryngeal dystonia and compare the values with normal controls. Twenty-one patients with adductor dystonia and 15 control patients underwent laryngeal electromyographic (EMG) examination of the left TA. We measured the latency from initiation spike of the electric activity of the TA muscle to the onset of phonation. Three speech-pathologists/voice specialists arrived at a consensus to rate the perceptual evaluation of voice quality for the study group. The average latency measured for patients with mild dysphonia was 332 milliseconds, for moderate dysphonia was 426 milliseconds, and for the severe dysphonia was 792 milliseconds. We used the Spearman's correlation test to compare the latency time values and the dysphonia's degree of severity (P<0.05). Latency was significantly and directly related to the degree of severity of dysphonia., (Copyright (c) 2010 The Voice Foundation. Published by Mosby, Inc. All rights reserved.)

Energy balance, including diet, weight, adiposity, and physical activity, is associated with carcinogenesis. Epidemiologic studies indicate that obesity and sedentary and/or active behavior are risk factors for breast cancer in postmenopausal women and survival in both premenopausal and postmenopausal breast cancer patients. Thus, understanding the influence of energy balance modulation on changes in gene expression patterns in the normal mammary gland is important for understanding mechanisms linking energy balance and breast cancer. In a 6-week-long study, female C57BL/6 mice (9-week-old) were randomized into four groups: (a) food consumed ad libitum (AL), (b) AL with access to running wheels (AL+EX), (c) 30% calorie restricted (CR), and (d) 30% CR with access to running wheels (CR+EX). CR mice received 70% of calories but 100% of all other nutrients compared with AL mice. Diet and exercise treatments, individually and combined, had significant effects on body composition and physical activity. Affymetrix oligomicroarrays were used to explore changes in gene expression patterns in total RNA samples from excised whole mammary glands. Contrasting AL versus CR resulted in 425 statistically significant expression changes, whereas AL versus AL+EX resulted in 45 changes, with only 3 changes included among the same genes, indicating that CR and EX differentially influence expression patterns in noncancerous mammary tissue. Differential expression was observed in genes related to breast cancer stem cells, the epithelial-mesenchymal transition, and the growth and survival of breast cancer cells. Thus, CR and EX seem to exert their effects on mammary carcinogenesis through distinct pathways.

The phonoarticulatory diadochokinesis test has been recommended to evaluate neurological disorders. It is a speech task that consists of the ability to repeat at high speed a segment of speech. The purpose of this research is to analyze the diadochokinesia rate of adults from two distinct age groups. 23 young adults and 23 elderly people, both sexes participated in this study. Each participant produced the /pa/, /ta/, /ka/ syllables, the vowel /a/ and the /pataka/ sequence, as fast and as long as they could with habitual pitch and loudness. The speech samples were analyzed by using the voice and speech analysis software Visi-Pitch III/Sona-Speech, KayElemetrics. Both groups presented with reduced diadochokinesia rate as the speech production became more complex. The young adults group presented with higher diadochokinesia rate in adults in all speech tasks while the elderly adults group had a worse intensity control.

Unlabelled: Dystonias are organic central motor processing disorders characterized by involuntary muscular contractions or incontrollable spasms induced by task-specific movements. Adduction laryngeal dystonias present with important speech impairments, with inappropriate spasms and abrupt voice breaks. The diagnosis is based on clinical features, evaluation by a speech therapist and transnasal fiber optic laryngoscopy., Aim: Our objective is to propose and evaluate a task-oriented transnasal fiber optic laryngoscopy protocol, which shows the spasms, and propose maneuvers that reduce or make them disappear, in order to facilitate the diagnosis., Methods: transversal study. Analysis of the transnasal fiber optic laryngoscopy records of 15 patients with adductor laryngeal dystonia using the proposed protocol., Results: most of the speech and non-vocal tasks allowed us to identify the spasms and reduce or make them disappear. We propose the exclusion of two of the maneuvers that dont bring new data to the evaluation., Conclusion: the protocol was useful for the evaluation of the patients, showing changes in muscle behavior in the structure under investigation.

Background: Gemcitabine has been recently recognized as standard treatment in advanced pancreatic cancer. To potentiate its single-agent activity we conducted a phase I-II study with the primary objective of establishing the maximum tolererated dose (MTD) of gemcitabine and continuous infusion 5-FU in patients with locally advanced or metastatic pancreatic cancer., Patients and Methods: Fifteen patients received a fired dose of 5-FU 200 mg/mq protracted infusion for six months. Gemcitabine was administered weekly for three out of four weeks for six cycles at escalating doses of 800 mg/mq to 1100 mg/mq., Results: MTD was established at 1000 mg/mq of gem citabine. Of the 11 evaluable patients, 7 patients had stable disease, 1 had partial response and 3 had progressive disease. Of the 14 patients evaluable at follow-up, median time to progression was 5 months. Median survival was 10 months., Conclusion: This study confirms the good tolerability of the combination, of gemcitabine with 5-FU.

Methyl alcohol was administered in drinking water supplied ad libitum at doses of 20,000, 5,000, 500, or 0 ppm to groups of male and female Sprague-Dawley rats 8 weeks old at the start of the experiment. Animals were kept under observation until spontaneous death. Ethyl alcohol was administered by ingestion in drinking water at a concentration of 10% or 0% supplied ad libitum to groups of male and female Sprague-Dawley rats; breeders and offspring were included in the experiment. Treatment started at 39 weeks of age (breeders), 7 days before mating, or from embryo life (offspring) and lasted until their spontaneous death. Under tested experimental conditions, methyl alcohol and ethyl alcohol were demonstrated to be carcinogenic for various organs and tissues. They must also be considered multipotential carcinogenic agents. In addition to causing other tumors, ethyl alcohol induced malignant tumors of the oral cavity, tongue, and lips. These sites have been shown to be target organs in man by epidemiologic studies.

Formaldehyde was administered for 104 weeks in drinking water supplied ad libitum at concentrations of 1500, 1000, 500, 100, 50, 10, or 0 mg/L to groups of 50 male and 50 female Sprague-Dawley rats beginning at seven weeks of age. Control animals (100 males and 100 females) received tap water only. Acetaldehyde was administered to 50 male and 50 female Sprague-Dawley rats beginning at six weeks of age at concentrations of 2,500, 1,500, 500, 250, 50, or 0 mg/L. Animals were kept under observation until spontaneous death. Formaldehyde and acetaldehyde were found to produce an increase in total malignant tumors in the treated groups and showed specific carcinogenic effects on various organs and tissues.

Proliferative activity has been proposed as a prognostic and predictive marker for breast cancer; Ki-67 is one of the most frequently used markers to assess proliferative activity. In the current study, Ki-67 immunoreactivity was comparatively assessed, even in terms prognostic relevance, with 3H-thymidine labeling index as a reference standard for proliferation in 126 patients with stage I and II breast cancer. There was a significant but weak correlation between Ki-67 values and the 3H-thymidine labeling index (r = 0.19, P = 0.03). Analysis of variance showed that the mean 3H-thymidine labeling index values were not statistically different in terms of pathologic size (T1, T2. T3, T4), number of pathologically positive axillary nodes (neg, pos 1-3, pos > 3), and grading classes (1, 2, 3), but significantly and inversely correlated with estrogen receptor status (P = 0.033) and progesterone receptor status (P = 0.08). The Ki-67 values significantly correlated with N status (P = 0.041), estrogen receptor status (P < 0.001), progesterone receptor status (P < 0.001), and grading (P < 0.001). The median follow-up was 37 months. In terms of prognosis, Ki-67 was associated significantly with overall survival (P = 0.01) and marginally with disease-free survival (P = 0.095). A significant difference in prognosis was found for both disease-free survival (P = 0.024) and overall survival (P = 0.040) when a 3H-thymidine labeling index cut-off of 6.5% was used (P = 0.024). The results suggest that, although both are indicators of proliferative activity, 3H-thymidine labeling index and Ki-67 seem to identify breast cancers with different phenotypes.

We report the case of a patient who was admitted in hospital for evaluation of a superior vena cava thrombosis. The patient exhibited an activated protein C resistance due to an arginine-506 mutation in factor V. Thoracic CT-scan showed a non-compressive complete superior vena cava thrombosis. Other investigations revealed a pleural effusion associated with an ovarian tumor. Pathological data of pleural biopsies showed a papillar carcinoma. Ovarian neoplasia revealed by a paraneoplasic syndrome was diagnosed. Treatment associated cyclophosphamide and carboplatin with anti-K-vitamin was administrated, with a complete remission and disappearance of superior vena cava thrombosis at 27 months of evolution. At this date, we observed a local pelvis recurrence which was treated with paclitaxel associated with surgery.

No single laboratory examination is diagnostic. On the other hand, such examinations support the diagnosis and aid in management of treated patients. In the serum, there is lymphopenia with a lowered CD4/CD8 ratio. An increase in beta 2-microglobulin and in the soluble IL-2 receptor reflect T lymphocyte activation. A classic observation is hypercalcaemia with hypercalciuria. The increase in angiotensin I converting enzyme reflects the body granulomatous mass. The results of bronchoalveolar lavage show the characteristics of the alveolitis associated with granulomatosis, accumulation of CD4+ T lymphocytes and activated alveolar macrophages. In practice, biochemical anomalies are of interest in the follow-up of treated patients.